Field of the Invention
This invention is directed to novel organic compounds and is more specifically concerned with new 2-[3-substituted-5-[(dimethylamino)methyl]-4H-1,2,4-triazol-4-yl]benzophen ones and a process of production therefor.
The novel compounds and the processes therefor can be illustratively represented as follows: ##STR5## wherein R'.sub.1 is hydroxymethyl or -CH.sub.2 NR.sub.6 R'.sub.7, in which R.sub.6 is -CH.sub.2 -C.tbd.CH, -CH.sub.2 -CH=CH.sub.2, or alkyl of 1 to 3 carbon atoms, inclusive, R'.sub.7 is alkyl of 1 to 3 carbon atoms, or together is pyrrolidino, piperidino or morpholino; wherein R.sub.2 is hydrogen, chlorine or fluorine; wherein R.sub.3 is hydrogen, or fluoro with the proviso that if R.sub.2 is chloro, R.sub.3 is not fluoro; wherein R.sub.4 is hydrogen, fluorine, chlorine, bromine, nitro, or trifluoromethyl; and wherein R.sub.5 is hydrogen, methyl or ethyl.
If a compound of formula IB ##STR6## wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are defined as above, is wanted, the following process II may be used: ##STR7## wherein R.sub.0 is an organic radical selected from alkyl of 1 to 3 carbon atoms, phenyl and p-tolyl, and wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 have the same values as hereinabove.
The compounds embraced by this invention can be presented by the formula I which combines structures IA and IB: ##STR8## wherein R.sub.1 is hydroxymethyl, or -CH.sub.2 NR.sub.6 R.sub.7, in which R.sub.6 is -CH.sub.2 -C.tbd.CH, -CH.sub.2 -CH=CH.sub.2, ##STR9## or alkyl of 1 to 3 carbon atoms, inclusive; R.sub.7 is hydrogen or alkyl of 1 to 3 carbon atoms; or together is pyrrolidino, piperidino or morpholino; wherein R.sub.2 is hydrogen, chlorine or fluorine; wherein R.sub.3 is hydrogen, or fluorine if R.sub.2 is fluorine; wherein R.sub.4 is hydrogen, fluorine, chlorine, bromine, nitro, or trifluoromethyl; and wherein R.sub.5 is hydrogen, methyl, or ethyl, and the pharmacological acid addition salts thereof.
The invention also includes the pharmacologically acceptable acid addition salts of the compounds of formula I.
The more desirable compounds of this invention have the formula IC: ##STR10## wherein R".sub.1 is hydroxymethyl or (dimethylamino)methyl; R.sub.2 is hydrogen, chlorine, or fluorine; R.sub.3 is hydrogen or fluorine if R.sub.2 is fluorine and R'.sub.4 is hydrogen, chlorine, or fluorine, and the pharmacologically acceptable acid addition salts thereof.
The most preferred compounds of this invention have the formula ID: ##STR11## wherein R".sub.1 is hydroxymethyl or (dimethylamino)methyl; and wherein R'.sub.2 and R".sub.4 are hydrogen or chlorine and the pharmacologically acceptable acid addition salts thereof.
The process I of this invention comprises: heating a compound of formula II in aqueous formic acid solution with 37% aqueous formaldehyde solution to give the corresponding compound of formula IA.
The process II of this invention comprises: treating a compound of formula IIA with formaldehyde in formic acid to obtain compound III; treating compound III with an organic sulfonyl chloride or an organic sulfonic anhydride with or without an added tertiary amine base to give compound IV; and treating compound IV with a primary amine to give the compound IB.